Mercapto derivatives of mercurated 1-pyridyl-3-allylureas



United States Patent 2,848,454 MERCAPTO DERIVATIVES 0F MERCI' m' ATED l-PYRIDYL-S-ALLYLUREAS John H. Biel, Milwaukee, Wis., assignor to-Ilakeside Laboratories, Inc., -a corporation-o Wisconsin No Drawing. Application June 4, 1956 Serial No. 588,998

'IDCIaims: C15- 260 -275) This'invention r'e'lates' to novel chemical eem' 'oan'as and processes of' preparing the same; More particularly, this invention relates to novel sulfur" containing mercury compounds; p A

this invention tliereare'pr'ovided' novel iircapro derivatives of mercuration products of l-pyridyl -iif-allylureas, which compounds have the formula matic mono and polycarboxylic acids, particularl'ywhere" the a'r'yl moiety is phenyl, lower alcohols, lower polyhydric alcohols, and salts thereof 1 p p Examples of particular residues which R'-S-' of the above formula may represent a're mereuewifiggrofips 2-mercaptobenzoic acid HO CHr-CH(OH) CHrS 2,3-dihydroxypropylmercapto The starting materials for producing these mercapto derivatives are 1-pyridyl-3-( 8-hydroxy or lower alkoxy- 'y-hyd-roxymerouri. propyl)-ureas, l-pyridyl-3-fl-hydroxy or lower al-koxy-y-ha-lomercuri propyl) -ureas and 1- pyridyl 3"-(j8-hydroxy or lower alkoxy-y-acyloxymercuri propyl)-ureas. The urea-moiety of the compounds may be joined 'at-the-a, p or 7 position' of the pyridyl group. Such compounds are disclosed in my copending application, Serial No. 588,999 filed June 4, 1956. In that applieation .it -is--disolosed that by reacting an aminopy'ridinc with allylisocyanate a 1-pyridy1-3-allylurea is formed which, upon reaction with a lower acyloxy mercury salt in water or a lower alcohol gives the corresponding 1- pyridyl-3-(p-hydr'oxy' or lower alkoxy y-acyloxymercuri propyl)-u'reaz. By." treatment of'the" acyloxynie'rcuride= riv'ativewitlran alk'alhhalide or alkalihydroxidethe corresponding hydroxymercuri and halomercuri compounds are formed. Representative of the starting materials which may be used in the subject invention are 1 (11- py'fridyI).-3-($-hydroxyw hydroxymercuri' propyl) -ui'ea, 1-(B-pyridyil). 3' '(li-methoxy-yacetoxymercuripro'pyl)'- urea, 1 ('y pyridyl) 3'- (fl-hydroxy-y-chloromercuri propyl)-urea and similar compounds in which the lower acyloxy gfoupsare" acetoxy, propio'nyloxy, butyrloxy and valeryloxy and the-lower alkoxy groups are methoxy, ethoxy, propionoxy, butoxy and amyloxy.

Tlie eompeunds of this-invention are" conveniently produced by contacting a starting material such as described above with a mercapto acid or a mercapto alcohol in a suitable solvent medium.

Di1i1'z'eqaqnebus;sbdium hydroxide may be "used as the reactionme'dium'for the merca'pto acids. The reac} use proceeds quickly at room temperature and is often completeddnh matterof minutes. Higher temperatures, with as *up" to'the'refiux" temperature, may b'e'e'rnployed; however to enhance reaction of the slowly-feactivemer c'apt'o a'cids Following termination of'the reactiomthe mixture is" usually'filtered; The basic reaction'mix'tu're gives salts of the reactiohprodu'cti Upon neutralization of the mixture the free acid is formed and precipitates;- It" is conveniently recovered and purified'by conventional procedures.

Although the mercapto alcohols may also be reacted in aqueous sodium hydroxide with the mercuri starting compound, it is often better to employ an organic solvent such as a lower alcohol, or other suitable solvent, in. theabsence of the base.- From; room to reflux tempera't ures may be employed according/to the-reactivity of particular reactants. v The desiredproduct-may precipi ta'te from 'the reaction mixture and can, therefore, be

recovered by filtration-g otherwise, it maybe -recovered by exaporating the mixture to dryness or other commorb procedures.

Approximately equimolar ratios of reactants are preferred altlioii'gdo'the'r ratios may a'ls'dbe used:

The compounds o'fthis invention form salts. Those compounds having carboxy groups form alkali metal salts, such-as sodium"and potassium salts, readilyupon contacting the acid and a suitable base in water. Ammonium salts are similarly prepared by the us'eof ammonium hydroxide. Salts are alsoformed with. amines such"asprocaine; cli'oline and the like;

The novel compounds'p'rovided by this-invention are poten't'diur'etic. agents which are effective" by' all routes as tablets, capsules and solutions may be formulated for the intended route of administration.

The following examples are presented to illustrate methods of producing certain of the novel compounds included within this invention. It is understood, however, that these examples are included only for purposes of illustration, and that the invention is not to be restricted to the embodiments specifically disclosed therein.

EXAMPLE 1 I (fl pyridyl) 3 ['y (1 -carbxyethylmercapto)-mercuri-fl-methoxypropyl] -urea WNHC ONHCHzCH(O CHQCHzHISCHUJHO-COzH To 4.7 g. (0.010 mole) of l-(fi-pyridyD-B-(B-methoxyy-acetoxymercuri propyl)-urea dissolved in 25 cc. of warm methanol was added 1.1 g. (0.010 mole) of thiolacetic acid. On seeding, a white crystalline precipitate was obtained; yield 3.9 g.; M. P. 121 C. sharp decomposition.

Analysis.-Calcd. for C H HgN O S: Hg, 39.1; N, 8.19; S, 6.23. Found: Hg, 38.5; N, 8.02; S, 6.08.

EXAMPLE 2 I (,3 pyridyl)-3-['y-(1,Z-dicarboxyethylmercapto)-mersari-,B-methoxypropyl] -urea To 4.7 g. (0.010 mole) of I-(fi-pyridyD-3-(fl-methoxy- 'y-acetoxymercuri propyl)-urea dissolved in 25 cc. of methanol was added 1.5 g. (0.010 mole) of thiomalic acid dissolved in methanol. A white, gummy precipitate resulted which was crystallized from acetone, yield 2.4 g., M. P. 80 C. dec.

Analysis.Calcd. for C H HgN O S: Hg, 34.7; N, 7.54; S, 5.73. Found: Hg, 35.9; N, 7.36; S, 4.91.

EXAMPLE 3 I (fl-pyria'yl) -3- ['y- 1 -th iosorb ityl) -mercuri-fi-methoxypropyl] -urea NH-C ONHCHQCIEHO CH1)CH1HK S 1-Sorbltyl To 4.7 g. (0.010 mole) of l-(fl-pyridyD-B-(B-methoxy- -acetoxymercuri propyl)-urea dissolved in 25 cc. of methanol was added 1.98 g. (0.010 mole) of l-thiosorbitol. After several days a crystalline precipitate appeared which was separated by filtration, M. P. 122 C. dec.

EXAMPLE 4 1 (18 pyridyl) 3 ['y (carboxymethylmercapto)-mercuri-fi-meth oxypropyl] -urea NHCONHCH:CH(O CHg) CHzHgSOHaC 01H Prepared as described in Example 1, from carboxymethyl mercapto, M. P. 125-126 C. dec.

Analysis.Calcd. fOI' C H HgN O S: Hg, N, 8.02; S, 6.08. Found: Hg, 38.8; N, 8.08; S, 6.53.

Various changes and modifications of the invention can be made and, to the extent that such variations incorporate the spirit of this invention, they are intended to be included within the scope of the appended claims.

What is claimed is:

1. A member of the group of compounds of the formula capto) -mercuri-p-methoxypropyl] -urea.

4. 1-pyridyl-3-['y-(dicarboxy-lower alkyl-mercapto)- mercuri-fi-lower alkoxy propyll-urea.

5. 1 (p pyridyl) 3 ['y (1,2-dicarboxyethyl-mercapto) -mercuri-fl-methoxypropyl] -urea.

6. 1 pyridyl 3-[y-(l-thiosorbityl)-mercuri-fi-lower alkoxy-propyll-urea.

7. 1 (p pyridyl) 3 ['ythiosorbityD-mercuri-pmethoxy-propylJ-urea.

8. 1 pyridyl 3-['y-(carboxy-lower mcrcuri-fl-lower alkoxy propyll-urea.

9. 1 (p pyridyl) 3 ['y-(carboxymethylmercapto)- mercuri-fi-methoxypropyl]-urea.

10. The process which comprises reacting a compound of the formula alkyl-mercapto)- with a member of the group consisting of lower mercaptan monocarboxylic acids, lower mercaptan polycarboxylic acids, phenyl mercaptan monocarboxylic acids, phenyl mercaptan polycarboxylic acids, lower mercaptan monohydric alcohols and lower mercaptan polyhydric alcohols to form a compound of the formula wherein in occurrence R is a member of the group consisting of hydrogen and lower alkyl groups, A is a member of the group consisting of halo, hydroxy and lower acyloxy groups, and R is a member of the group consisting of monocarboxy substituted lower alkyl groups, polycarboxy substituted lower alkyl groups, monocarboxy substituted phenyl groups, polycarboxy substituted phenyl groups, lower monohydric alcohol groups and lower polyhydric. alcohol groups.

References Cited in the file of this patent UNITED STATES PATENTS 2,635,982 Rowland Apr. 21, 1953 

1. A MEMBER OF THE GROUP OF COMPOUNDS OF THE FORMULA 